The engineering of multicellular organotypic models of the human intestinal mucosa has wide-ranging potential as a tool for discovery in both health and disease, including interaction with pathogens, antigen trafficking, inflammatory and physiological processes as well as tissue bioengineering. However, models reported to date remain relatively simple composed of few cell types. In particular, prior models consist of: (1) small fragments of human primary tissues which can be maintained in vitro for a very short time, or (2) bioengineered tissues composed of a few different cell types, mainly epithelial cells and fibroblasts, but lacking other stromal cells (e.g., immune cells such as lymphocytes, macrophages and dendritic cells).
For example, U.S. Pat. No. 7,244,578 (Hammond), which is hereby incorporated herein by reference, provides methods for utilizing a form of suspension culture to examine infectivity of pathogenic organisms and agents. But among the many disadvantages of Hammond, Hammond uses extracellular matrix beads, which cannot be manipulated. Cells cannot be incorporated on the ECM of Hammond, and therefore Hammond's model cannot result in a multicellular ECM.
To more appropriately mimic an in vivo microenvironment, 3-dimensional cell culture models need to assume a more complex cellular architecture and functionalities which more closely resemble those observed in native tissues.